KIF1B and NF1 are the most frequently mutated genes in paraganglioma and pheochromocytoma tumors

Dear Editor, Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors arising from the adrenal medulla and extra-adrenal paraganglia, respectively. Forty percent are explained by germline mutations in known susceptibility genes. Furthermore, somatic mutations were identified in an additional 30% of PPGL, mostly in NF1, RET, VHL, MAX, and HRAS. However, screening is limited to a few studies mainly using Sanger sequencing (Burnichon, et al. 2012; Burnichon, et al. 2011; Crona, et al. 2013; Luchetti, et al. 2015; Stenman, et al. 2016; Weber, et al. 2012; Welander, et al. 2012). Our aim was to look for the prevalence and nature of somatic mutations using a targeted deep-sequencing approach in patients from a Belgian multicentric PPGL cohort. Targeted Next Generation Sequencing was performed in 74 tumors using a panel including 17 susceptibility genes. Variants considered as damaging by at least 5 prediction programs, or present in COSMIC and considered as damaging by at least 3 prediction programs, were considered to be disease-associated mutations. Somatic mutations were identified in 54% of patients. The most frequently mutated genes were NF1 (20.8%) and KIF1B (20.4%). While the high prevalence of somatic mutations in NF1 is in agreement with previous studies, the similarly elevated prevalence of mutations in KIF1B is novel.